Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. Pain is classified according to cause into nociceptive pain, neuropathic pain and psychogenic pain. As pain caused by an unknown cause, fibromyalgia syndrome is known.
The neuropathic pain is pathological pain caused by peripheral or central nervous system dysfunction, more specifically, pain caused by, e.g., direct damage and oppression of the nerve tissue despite of no nociceptive stimulus to a nociceptor. As a therapeutic agent for neuropathic pain, an anticonvulsant, an antidepressant, an anxiolytic drug or an antiepileptic drug such as gabapentin or pregabalin is used.
Fibromyalgia syndrome is a disorder in which systemic pain is a leading symptom and neuropsychiatric and neurovegetative symptoms are secondary symptoms. As therapeutic agents for fibromyalgia syndrome, pregabalin, which has been approved in the United States and Japan, duloxetine and milnacipran, which have been approved in the United States, are principally used. Also, drugs not approved as a therapeutic agent for fibromyalgia syndrome, i.e., a nonsteroidal anti-inflammatory agent, an opioid compound, an antidepressant, an anticonvulsant and an antiepileptic drug are used. However, nonsteroidal anti-inflammatory agents and opioid compounds are generally said to have a low therapeutic effect (Recla, Journal of Pain Research, Vol. 3, pp 89-103, 2010).
Other than these, French Patent 2 567 885 discloses that substituted piperidines have a cardiotonic activity; JP Patent Publication (Kokai) No. 2006-008664 discloses that imidazole derivatives have an FXa inhibitory effect; and International Publication WO 2003/031432 suggests that substituted piperidines have a potential drug efficacy against overweight or obesity.
However, therapy with a conventional therapeutic agent for neuropathic pain is highly frequently associated with central nervous system adverse drug reactions such as dizziness, nausea or vomiting. Because of this, it is difficult to administer a conventional therapeutic agent for a long-term. In the context, development of a novel therapeutic agent for neuropathic pain has been desired.
Even pregabalin, duloxetine and milnacipran, which have been approved as therapeutic agents for fibromyalgia syndrome, fail to provide clinically satisfactory therapeutic effect against fibromyalgia syndrome and their drug efficacy significantly varies among patients. In that context, it has been strongly desired to develop a novel therapeutic agent for fibromyalgia syndrome exerting a sufficient therapeutic effect.
Note that, FR '885 suggests that the substituted piperidines described therein have efficacy for migraine. However, it does not suggest the relevancy of analgesic action to a chemical structure. JP '664 which describes imidazole derivatives and WO '432 which describes substituted piperidines neither disclose nor suggest potentiality of analgesic action of those compounds.
It could therefore be helpful to provide a compound having a strong analgesic action for pain, in particular, neuropathic pain and/or fibromyalgia syndrome.